Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review.

Sonia Franchini,Yagmur Esemen,Ilaria Masala,Arsalan Baig,Rabeeia Parwez,Mariam Awan,Dimitrios Giakoumettis,Shahinur Rahman

doi:10.3390/ijms23052607

Sonia Franchini, Yagmur Esemen + Show 6 more

Open Access

https://doi.org/10.3390/ijms23052607

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Abstract

Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.

Highlights

Glioma is an umbrella term used to describe primary brain tumours
Four articles discussing the receptor kinases (RTK)/RAS pathway were analysed, and two studies highlighted the role of CIC as a tumour suppressor protein whereby preventing degradation or inhibition sensitised GBM cells to its anti-tumorigenic effects [42,43]
Four studies relating to the RB pathway were used in this review, two of which examined the use of cyclin-dependent kinases (CDK) inhibitors in clinical trials, showing these agents to be ineffective monotherapy due to lack of progression free survival [44,45]

Summary

Introduction

Glioma is an umbrella term used to describe primary brain tumours. GlioblastomaMultiforme (GBM) is the commonest glioma in adults, and it accounts for more than 60%of all adult brain tumours [1]. Multiforme (GBM) is the commonest glioma in adults, and it accounts for more than 60%. International incidence of glioma is reported as 5.3 per 100,000 population per year and seems to be higher in the Western world [3]. Glioblastoma multiforme remains a notoriously hard to treat cancer associated with treatment resistance and high recurrence rates. Gliomagenesis, the formation and development of gliomas, is a multistep process in which normal cells undergo genetic alterations that lead to malignant derivatives [9]. Cells progressively acquire genetic and epigenetic changes resulting in inhibiting tumour suppressor genes (TSG) and activation of proto-oncogenes. Together, these changes help cells escape the body’s regulatory mechanisms and lead to rapidly proliferating, undifferentiated cell clusters, known as tumours. These tumours become malignant when they invade and migrate into other tissues

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